HRP20220502T1 - Kombinacije koje sadrže derivate 5-fenoksi-3h-pirimidin-4-ona i njihova uporaba za profilaksu ili liječenje infekcije hiv-om - Google Patents
Kombinacije koje sadrže derivate 5-fenoksi-3h-pirimidin-4-ona i njihova uporaba za profilaksu ili liječenje infekcije hiv-om Download PDFInfo
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- HRP20220502T1 HRP20220502T1 HRP20220502TT HRP20220502T HRP20220502T1 HR P20220502 T1 HRP20220502 T1 HR P20220502T1 HR P20220502T T HRP20220502T T HR P20220502TT HR P20220502 T HRP20220502 T HR P20220502T HR P20220502 T1 HRP20220502 T1 HR P20220502T1
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- Prior art keywords
- alkyl
- haloalkyl
- independently
- substituents
- ariq
- Prior art date
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- 238000011321 prophylaxis Methods 0.000 title claims 3
- PRXCVXCFQYBCQL-UHFFFAOYSA-N 5-phenoxy-1h-pyrimidin-6-one Chemical class OC1=NC=NC=C1OC1=CC=CC=C1 PRXCVXCFQYBCQL-UHFFFAOYSA-N 0.000 title 1
- 208000015181 infectious disease Diseases 0.000 title 1
- 238000011282 treatment Methods 0.000 title 1
- 229910052757 nitrogen Inorganic materials 0.000 claims 45
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 41
- 229910052799 carbon Inorganic materials 0.000 claims 33
- 125000001424 substituent group Chemical group 0.000 claims 30
- 229910052736 halogen Inorganic materials 0.000 claims 11
- 150000002367 halogens Chemical class 0.000 claims 11
- 125000005842 heteroatom Chemical group 0.000 claims 10
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 9
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 8
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 8
- 150000001875 compounds Chemical class 0.000 claims 7
- 150000003839 salts Chemical class 0.000 claims 7
- 101100059444 Mus musculus Ccnb1 gene Proteins 0.000 claims 6
- 229920006395 saturated elastomer Polymers 0.000 claims 6
- 229940124411 anti-hiv antiviral agent Drugs 0.000 claims 5
- 125000003118 aryl group Chemical group 0.000 claims 5
- 229910052760 oxygen Inorganic materials 0.000 claims 5
- 229910052717 sulfur Inorganic materials 0.000 claims 5
- 125000000217 alkyl group Chemical group 0.000 claims 4
- 239000002259 anti human immunodeficiency virus agent Substances 0.000 claims 4
- 125000001072 heteroaryl group Chemical group 0.000 claims 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 3
- 208000030507 AIDS Diseases 0.000 claims 3
- 125000004432 carbon atom Chemical group C* 0.000 claims 3
- 125000004122 cyclic group Chemical group 0.000 claims 3
- WHBIGIKBNXZKFE-UHFFFAOYSA-N delavirdine Chemical compound CC(C)NC1=CC=CN=C1N1CCN(C(=O)C=2NC3=CC=C(NS(C)(=O)=O)C=C3C=2)CC1 WHBIGIKBNXZKFE-UHFFFAOYSA-N 0.000 claims 3
- 125000000623 heterocyclic group Chemical group 0.000 claims 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 3
- 229960004693 tenofovir disoproxil fumarate Drugs 0.000 claims 3
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 2
- 125000000081 (C5-C8) cycloalkenyl group Chemical group 0.000 claims 2
- VERWQPYQDXWOGT-LVJNJWHOSA-N 4-amino-5-fluoro-1-[(2r,5s)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]pyrimidin-2-one;[[(2r)-1-(6-aminopurin-9-yl)propan-2-yl]oxymethyl-(propan-2-yloxycarbonyloxymethoxy)phosphoryl]oxymethyl propan-2-yl carbonate;(e)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.C1=C(F)C(N)=NC(=O)N1[C@H]1O[C@@H](CO)SC1.N1=CN=C2N(C[C@@H](C)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C)C=NC2=C1N VERWQPYQDXWOGT-LVJNJWHOSA-N 0.000 claims 2
- 108010019625 Atazanavir Sulfate Proteins 0.000 claims 2
- 102100024170 Cyclin-C Human genes 0.000 claims 2
- BXZVVICBKDXVGW-NKWVEPMBSA-N Didanosine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(NC=NC2=O)=C2N=C1 BXZVVICBKDXVGW-NKWVEPMBSA-N 0.000 claims 2
- XPOQHMRABVBWPR-UHFFFAOYSA-N Efavirenz Natural products O1C(=O)NC2=CC=C(Cl)C=C2C1(C(F)(F)F)C#CC1CC1 XPOQHMRABVBWPR-UHFFFAOYSA-N 0.000 claims 2
- 208000031886 HIV Infections Diseases 0.000 claims 2
- 108010078851 HIV Reverse Transcriptase Proteins 0.000 claims 2
- 208000037357 HIV infectious disease Diseases 0.000 claims 2
- 101000980770 Homo sapiens Cyclin-C Proteins 0.000 claims 2
- 101100273648 Mus musculus Ccna2 gene Proteins 0.000 claims 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims 2
- UGWQMIXVUBLMAH-IVVFTGHFSA-N [(1s,4r)-4-[2-amino-6-(cyclopropylamino)purin-9-yl]cyclopent-2-en-1-yl]methanol;4-amino-1-[(2r,5s)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]pyrimidin-2-one Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1.C=12N=CN([C@H]3C=C[C@@H](CO)C3)C2=NC(N)=NC=1NC1CC1 UGWQMIXVUBLMAH-IVVFTGHFSA-N 0.000 claims 2
- 125000003342 alkenyl group Chemical group 0.000 claims 2
- 125000004429 atom Chemical group 0.000 claims 2
- 125000002619 bicyclic group Chemical group 0.000 claims 2
- 125000004452 carbocyclyl group Chemical group 0.000 claims 2
- 229960002656 didanosine Drugs 0.000 claims 2
- 229960003804 efavirenz Drugs 0.000 claims 2
- XPOQHMRABVBWPR-ZDUSSCGKSA-N efavirenz Chemical compound C([C@]1(C2=CC(Cl)=CC=C2NC(=O)O1)C(F)(F)F)#CC1CC1 XPOQHMRABVBWPR-ZDUSSCGKSA-N 0.000 claims 2
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims 2
- IKKXOSBHLYMWAE-QRPMWFLTSA-N islatravir Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@H]1C[C@H](O)[C@](CO)(C#C)O1 IKKXOSBHLYMWAE-QRPMWFLTSA-N 0.000 claims 2
- 125000002950 monocyclic group Chemical group 0.000 claims 2
- 125000001624 naphthyl group Chemical group 0.000 claims 2
- NQDJXKOVJZTUJA-UHFFFAOYSA-N nevirapine Chemical compound C12=NC=CC=C2C(=O)NC=2C(C)=CC=NC=2N1C1CC1 NQDJXKOVJZTUJA-UHFFFAOYSA-N 0.000 claims 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 2
- 125000006574 non-aromatic ring group Chemical group 0.000 claims 2
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 claims 2
- 229960002555 zidovudine Drugs 0.000 claims 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
- 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims 1
- YSIBYEBNVMDAPN-CMDGGOBGSA-N (e)-4-oxo-4-(3-triethoxysilylpropylamino)but-2-enoic acid Chemical compound CCO[Si](OCC)(OCC)CCCNC(=O)\C=C\C(O)=O YSIBYEBNVMDAPN-CMDGGOBGSA-N 0.000 claims 1
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 claims 1
- NUBQKPWHXMGDLP-UHFFFAOYSA-N 1-[4-benzyl-2-hydroxy-5-[(2-hydroxy-2,3-dihydro-1h-inden-1-yl)amino]-5-oxopentyl]-n-tert-butyl-4-(pyridin-3-ylmethyl)piperazine-2-carboxamide;sulfuric acid Chemical compound OS(O)(=O)=O.C1CN(CC(O)CC(CC=2C=CC=CC=2)C(=O)NC2C3=CC=CC=C3CC2O)C(C(=O)NC(C)(C)C)CN1CC1=CC=CN=C1 NUBQKPWHXMGDLP-UHFFFAOYSA-N 0.000 claims 1
- HUTNOYOBQPAKIA-UHFFFAOYSA-N 1h-pyrazin-2-one Chemical compound OC1=CN=CC=N1 HUTNOYOBQPAKIA-UHFFFAOYSA-N 0.000 claims 1
- AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical compound OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 claims 1
- QMNWYGTWTXOQTP-UHFFFAOYSA-N 1h-triazin-6-one Chemical compound O=C1C=CN=NN1 QMNWYGTWTXOQTP-UHFFFAOYSA-N 0.000 claims 1
- LHCOVOKZWQYODM-CPEOKENHSA-N 4-amino-1-[(2r,5s)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]pyrimidin-2-one;1-[(2r,4s,5s)-4-azido-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1.O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 LHCOVOKZWQYODM-CPEOKENHSA-N 0.000 claims 1
- YCIPQJTZJGUXND-UHFFFAOYSA-N Aglaia odorata Alkaloid Natural products C1=CC(OC)=CC=C1C1(C(C=2C(=O)N3CCCC3=NC=22)C=3C=CC=CC=3)C2(O)C2=C(OC)C=C(OC)C=C2O1 YCIPQJTZJGUXND-UHFFFAOYSA-N 0.000 claims 1
- AXRYRYVKAWYZBR-UHFFFAOYSA-N Atazanavir Natural products C=1C=C(C=2N=CC=CC=2)C=CC=1CN(NC(=O)C(NC(=O)OC)C(C)(C)C)CC(O)C(NC(=O)C(NC(=O)OC)C(C)(C)C)CC1=CC=CC=C1 AXRYRYVKAWYZBR-UHFFFAOYSA-N 0.000 claims 1
- QAGYKUNXZHXKMR-UHFFFAOYSA-N CPD000469186 Natural products CC1=C(O)C=CC=C1C(=O)NC(C(O)CN1C(CC2CCCCC2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-UHFFFAOYSA-N 0.000 claims 1
- XQSPYNMVSIKCOC-NTSWFWBYSA-N Emtricitabine Chemical compound C1=C(F)C(N)=NC(=O)N1[C@H]1O[C@@H](CO)SC1 XQSPYNMVSIKCOC-NTSWFWBYSA-N 0.000 claims 1
- 108010032976 Enfuvirtide Proteins 0.000 claims 1
- 229940099797 HIV integrase inhibitor Drugs 0.000 claims 1
- KJHKTHWMRKYKJE-SUGCFTRWSA-N Kaletra Chemical compound N1([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=2C=CC=CC=2)NC(=O)COC=2C(=CC=CC=2C)C)CC=2C=CC=CC=2)CCCNC1=O KJHKTHWMRKYKJE-SUGCFTRWSA-N 0.000 claims 1
- OFFWOVJBSQMVPI-RMLGOCCBSA-N Kaletra Chemical compound N1([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=2C=CC=CC=2)NC(=O)COC=2C(=CC=CC=2C)C)CC=2C=CC=CC=2)CCCNC1=O.N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 OFFWOVJBSQMVPI-RMLGOCCBSA-N 0.000 claims 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims 1
- 229940122313 Nucleoside reverse transcriptase inhibitor Drugs 0.000 claims 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 1
- NCDNCNXCDXHOMX-UHFFFAOYSA-N Ritonavir Natural products C=1C=CC=CC=1CC(NC(=O)OCC=1SC=NC=1)C(O)CC(CC=1C=CC=CC=1)NC(=O)C(C(C)C)NC(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-UHFFFAOYSA-N 0.000 claims 1
- IRHXGOXEBNJUSN-YOXDLBRISA-N Saquinavir mesylate Chemical compound CS(O)(=O)=O.C([C@@H]([C@H](O)CN1C[C@H]2CCCC[C@H]2C[C@H]1C(=O)NC(C)(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)C=1N=C2C=CC=CC2=CC=1)C1=CC=CC=C1 IRHXGOXEBNJUSN-YOXDLBRISA-N 0.000 claims 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
- SUJUHGSWHZTSEU-UHFFFAOYSA-N Tipranavir Natural products C1C(O)=C(C(CC)C=2C=C(NS(=O)(=O)C=3N=CC(=CC=3)C(F)(F)F)C=CC=2)C(=O)OC1(CCC)CCC1=CC=CC=C1 SUJUHGSWHZTSEU-UHFFFAOYSA-N 0.000 claims 1
- WREGKURFCTUGRC-POYBYMJQSA-N Zalcitabine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)CC1 WREGKURFCTUGRC-POYBYMJQSA-N 0.000 claims 1
- 229960004748 abacavir Drugs 0.000 claims 1
- MCGSCOLBFJQGHM-SCZZXKLOSA-N abacavir Chemical compound C=12N=CN([C@H]3C=C[C@@H](CO)C3)C2=NC(N)=NC=1NC1CC1 MCGSCOLBFJQGHM-SCZZXKLOSA-N 0.000 claims 1
- 229960000531 abacavir sulfate Drugs 0.000 claims 1
- WMHSRBZIJNQHKT-FFKFEZPRSA-N abacavir sulfate Chemical compound OS(O)(=O)=O.C=12N=CN([C@H]3C=C[C@@H](CO)C3)C2=NC(N)=NC=1NC1CC1.C=12N=CN([C@H]3C=C[C@@H](CO)C3)C2=NC(N)=NC=1NC1CC1 WMHSRBZIJNQHKT-FFKFEZPRSA-N 0.000 claims 1
- 229960001830 amprenavir Drugs 0.000 claims 1
- YMARZQAQMVYCKC-OEMFJLHTSA-N amprenavir Chemical compound C([C@@H]([C@H](O)CN(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)NC(=O)O[C@@H]1COCC1)C1=CC=CC=C1 YMARZQAQMVYCKC-OEMFJLHTSA-N 0.000 claims 1
- 229960005475 antiinfective agent Drugs 0.000 claims 1
- 239000004599 antimicrobial Substances 0.000 claims 1
- 239000003443 antiviral agent Substances 0.000 claims 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims 1
- 229960003277 atazanavir Drugs 0.000 claims 1
- AXRYRYVKAWYZBR-GASGPIRDSA-N atazanavir Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)[C@@H](O)CN(CC=1C=CC(=CC=1)C=1N=CC=CC=1)NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)C1=CC=CC=C1 AXRYRYVKAWYZBR-GASGPIRDSA-N 0.000 claims 1
- 229960003796 atazanavir sulfate Drugs 0.000 claims 1
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims 1
- 229910052794 bromium Inorganic materials 0.000 claims 1
- PMDQGYMGQKTCSX-HQROKSDRSA-L calcium;[(2r,3s)-1-[(4-aminophenyl)sulfonyl-(2-methylpropyl)amino]-3-[[(3s)-oxolan-3-yl]oxycarbonylamino]-4-phenylbutan-2-yl] phosphate Chemical compound [Ca+2].C([C@@H]([C@H](OP([O-])([O-])=O)CN(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)NC(=O)O[C@@H]1COCC1)C1=CC=CC=C1 PMDQGYMGQKTCSX-HQROKSDRSA-L 0.000 claims 1
- 229950008230 capravirine Drugs 0.000 claims 1
- YQXCVAGCMNFUMQ-UHFFFAOYSA-N capravirine Chemical compound C=1C(Cl)=CC(Cl)=CC=1SC1=C(C(C)C)N=C(COC(N)=O)N1CC1=CC=NC=C1 YQXCVAGCMNFUMQ-UHFFFAOYSA-N 0.000 claims 1
- 229910052801 chlorine Inorganic materials 0.000 claims 1
- 125000000392 cycloalkenyl group Chemical group 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 229960005107 darunavir Drugs 0.000 claims 1
- CJBJHOAVZSMMDJ-HEXNFIEUSA-N darunavir Chemical compound C([C@@H]([C@H](O)CN(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)NC(=O)O[C@@H]1[C@@H]2CCO[C@@H]2OC1)C1=CC=CC=C1 CJBJHOAVZSMMDJ-HEXNFIEUSA-N 0.000 claims 1
- 229960005319 delavirdine Drugs 0.000 claims 1
- 229960000475 delavirdine mesylate Drugs 0.000 claims 1
- MEPNHSOMXMALDZ-UHFFFAOYSA-N delavirdine mesylate Chemical compound CS(O)(=O)=O.CC(C)NC1=CC=CN=C1N1CCN(C(=O)C=2NC3=CC=C(NS(C)(=O)=O)C=C3C=2)CC1 MEPNHSOMXMALDZ-UHFFFAOYSA-N 0.000 claims 1
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims 1
- IPZJQDSFZGZEOY-UHFFFAOYSA-N dimethylmethylene Chemical compound C[C]C IPZJQDSFZGZEOY-UHFFFAOYSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 229960000366 emtricitabine Drugs 0.000 claims 1
- PEASPLKKXBYDKL-FXEVSJAOSA-N enfuvirtide Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(C)=O)[C@@H](C)O)[C@@H](C)CC)C1=CN=CN1 PEASPLKKXBYDKL-FXEVSJAOSA-N 0.000 claims 1
- 229960002062 enfuvirtide Drugs 0.000 claims 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims 1
- 229960002049 etravirine Drugs 0.000 claims 1
- PYGWGZALEOIKDF-UHFFFAOYSA-N etravirine Chemical compound CC1=CC(C#N)=CC(C)=C1OC1=NC(NC=2C=CC(=CC=2)C#N)=NC(N)=C1Br PYGWGZALEOIKDF-UHFFFAOYSA-N 0.000 claims 1
- 229910052731 fluorine Inorganic materials 0.000 claims 1
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- 230000004927 fusion Effects 0.000 claims 1
- 239000002835 hiv fusion inhibitor Substances 0.000 claims 1
- 239000003084 hiv integrase inhibitor Substances 0.000 claims 1
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- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000002955 immunomodulating agent Substances 0.000 claims 1
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- 229960001936 indinavir Drugs 0.000 claims 1
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- 230000002401 inhibitory effect Effects 0.000 claims 1
- 229960001627 lamivudine Drugs 0.000 claims 1
- JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 claims 1
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- GSNHKUDZZFZSJB-QYOOZWMWSA-N maraviroc Chemical compound CC(C)C1=NN=C(C)N1[C@@H]1C[C@H](N2CC[C@H](NC(=O)C3CCC(F)(F)CC3)C=3C=CC=CC=3)CC[C@H]2C1 GSNHKUDZZFZSJB-QYOOZWMWSA-N 0.000 claims 1
- KHASNRBNVBIREH-IZEXYCQBSA-N methyl n-[(2s)-1-[[(5s)-5-[(4-aminophenyl)sulfonyl-(2-methylpropyl)amino]-6-phosphonooxyhexyl]amino]-1-oxo-3,3-diphenylpropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C([C@H](NC(=O)OC)C(=O)NCCCC[C@@H](COP(O)(O)=O)N(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)C1=CC=CC=C1 KHASNRBNVBIREH-IZEXYCQBSA-N 0.000 claims 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 1
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- QAGYKUNXZHXKMR-HKWSIXNMSA-N nelfinavir Chemical compound CC1=C(O)C=CC=C1C(=O)N[C@H]([C@H](O)CN1[C@@H](C[C@@H]2CCCC[C@@H]2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-HKWSIXNMSA-N 0.000 claims 1
- 229960005230 nelfinavir mesylate Drugs 0.000 claims 1
- NQHXCOAXSHGTIA-SKXNDZRYSA-N nelfinavir mesylate Chemical compound CS(O)(=O)=O.CC1=C(O)C=CC=C1C(=O)N[C@H]([C@H](O)CN1[C@@H](C[C@@H]2CCCC[C@@H]2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 NQHXCOAXSHGTIA-SKXNDZRYSA-N 0.000 claims 1
- 229960000689 nevirapine Drugs 0.000 claims 1
- 239000002777 nucleoside Substances 0.000 claims 1
- 150000003833 nucleoside derivatives Chemical class 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims 1
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 claims 1
- 229960004742 raltegravir Drugs 0.000 claims 1
- CZFFBEXEKNGXKS-UHFFFAOYSA-N raltegravir Chemical compound O1C(C)=NN=C1C(=O)NC(C)(C)C1=NC(C(=O)NCC=2C=CC(F)=CC=2)=C(O)C(=O)N1C CZFFBEXEKNGXKS-UHFFFAOYSA-N 0.000 claims 1
- 229960000311 ritonavir Drugs 0.000 claims 1
- NCDNCNXCDXHOMX-XGKFQTDJSA-N ritonavir Chemical compound N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-XGKFQTDJSA-N 0.000 claims 1
- 229960001852 saquinavir Drugs 0.000 claims 1
- QWAXKHKRTORLEM-UGJKXSETSA-N saquinavir Chemical compound C([C@@H]([C@H](O)CN1C[C@H]2CCCC[C@H]2C[C@H]1C(=O)NC(C)(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)C=1N=C2C=CC=CC2=CC=1)C1=CC=CC=C1 QWAXKHKRTORLEM-UGJKXSETSA-N 0.000 claims 1
- 229960003542 saquinavir mesylate Drugs 0.000 claims 1
- -1 stavudin Chemical compound 0.000 claims 1
- 229960004556 tenofovir Drugs 0.000 claims 1
- VCMJCVGFSROFHV-WZGZYPNHSA-N tenofovir disoproxil fumarate Chemical compound OC(=O)\C=C\C(O)=O.N1=CN=C2N(C[C@@H](C)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C)C=NC2=C1N VCMJCVGFSROFHV-WZGZYPNHSA-N 0.000 claims 1
- 229960000838 tipranavir Drugs 0.000 claims 1
- SUJUHGSWHZTSEU-FYBSXPHGSA-N tipranavir Chemical compound C([C@@]1(CCC)OC(=O)C([C@H](CC)C=2C=C(NS(=O)(=O)C=3N=CC(=CC=3)C(F)(F)F)C=CC=2)=C(O)C1)CC1=CC=CC=C1 SUJUHGSWHZTSEU-FYBSXPHGSA-N 0.000 claims 1
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims 1
- 229960000523 zalcitabine Drugs 0.000 claims 1
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 claims 1
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- C07D471/04—Ortho-condensed systems
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- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
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- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/52—Two oxygen atoms
- C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
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- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
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Claims (15)
1. Kombinacija koja sadrži (i) spoj formule (Ia):
[image]
ili njegovu farmaceutski prihvatljivu sol i (ii) jedno ili više sredstava protiv HIV-a izabranih od antivirusnih sredstava protiv HIV-a, imunomodulatora i anti-infektivnih sredstava, gdje:
M je CH2, CH2CH2, CH2CH2CH2, CH(CH3), C(CH3)2 ili C(O)N(RA);
Z je izabran iz grupe koja se sastoji od: piridazina, piridazinona, pirimidina, pirimidinona, pirazina, pirazinona, triazina i triazinona, svaki izborno supstituiran sa jednim ili više supstituenata do maksimalnog broja dozvoljenog valentnošću izabranog od R4 i R5;
svaki K1 i K2 su neovisno F, Br, Cl, OCHF2, CF3 ili CN;
R2 je izabran iz grupe koja se sastoji od:
(1) H,
(2) C1-6 alkila,
(3) C1-6 haloalkila,
(4) C1-6 alkila supstituiranog sa od 1 do 3 supstituenta od kojih je svaki neovisno OH, O-C1-6 alkil, O-C1-6 haloalkil, CN, NO2, N(RA)RB, C(O)N(RA)RB, C(O)RA, CO2RA, SRA, S(O)RA, S(O)2RA, S(O)2N(RA)RB, N(RA)C(O)RB, N(RA)CO2RB, N(RA)S(O)2RB, N(RA)S(O)2N(RA)RB, OC(O)N(RA)RB, N(RA)C(O)N(RA)RB ili N(RA)C(O)C(O)N(RA)RB,
(5) O-C1-6 alkila u kojem je alkil izborno supstituiran sa 1 do 3 supstituenta neovisno izabrana od OH, O-C1-6 alkila, O-C1-6 haloalkila, CN, N(RA)RB, C(O)N(RA)RB, C(O)RA, CO2RA, SRA, S(O)RA, S(O)2RA, ili S(O)2N(RA)RB,
(6) O-C1-6 haloalkila,
(7) halogena,
(8) CN,
(9) NO2,
(10) N(RA)RB,
(11) C(O)N(RA)RB,
(12) C(O)RA,
(13) C(O)-C1-6 haloalkila,
(14) C(O)ORA,
(15) OC(O)RA,
(16) OC(O)N(RA)RB,
(17) SRA,
(18) S(O)RA,
(19) S(O)2RA,
(20) S(O)2N(RA)RB,
(21) N(RA)S(O)2RB,
(22) N(RA)S(O)2N(RA)RB,
(23) N(RA)C(O)RB,
(24) N(RA)C(O)N(RA)RB,
(25) N(RA)C(O)-C(O)N(RA)RB,
(26) N(RA)CO2RB,
(27) N(RC)RD,
(28) C(O)N(RC)RD,
(29) OC(O)N(RC)RD,
(30) S(O)2N(RC)RD,
(31) N(RA)S(O)2N(RC)RD,
(32) N(RA)C(O)N(RC)RD,
(33) N(RA)C(O)-C(O)N(RC)RD,
(34) CycA,
(35) -O-CycA,
(36) ArilA, ili
(37) HetA;
R3 je H, C1-6 alkil, halogen, CN, C1-6 fluoroalkil, OH, O-C1-6 alkil ili O-C1-6 haloalkil;
R4 i R5 su svaki neovisno izabrani od:
(1) H,
(2) C1-6 alkila, C2-6 alkenila ili C2-6 alkinila, svaki izborno supstituiran sa jednim ili više supstituenata do maksimalnog broja dozvoljenog valentnošću izabranog od OH, O-C1-6 alkila, O-C1-6 haloalkila, CN, NO2, N(RA)RB, C(O)N(RA)RB, C(O)RA, CO2RA, SRA, S(O)RA, S(O)2RA, S(O)2N(RA)RB, N(RA)C(O)RB, N(RA)CO2RB, N(RA)S(O)2RB, N(RA)S(O)2N(RA)RB, OC(O)N(RA)RB, N(RA)C(O)N(RA)RB, N(RA)C(O)C(O)N(RA)RB, CycB, ArilB i HetB,
(3) C1-6 haloalkila izborno dodatno supstituiranog sa jednim ili više supstituenata do maksimalnog broja dozvoljenog valentnošću izabranog od OH, O-C1-6 alkila, O-C1-6 haloalkila, CN, NO2, N(RA)RB, C(O)N(RA)RB, C(O)RA, CO2RA, SRA, S(O)RA, S(O)2RA, S(O)2N(RA)RB, N(RA)C(O)RB, N(RA)CO2RB, N(RA)S(O)2RB, N(RA)S(O)2N(RA)RB, OC(O)N(RA)RB, N(RA)C(O)N(RA)RB, N(RA)C(O)C(O)N(RA)RB, CycB, ArilB i HetB
(4) O-C1-6 alkila u kojem je dio alkila izborno supstituiran sa jednim ili više supstituenata do maksimalnog broja dozvoljenog valentnošću izabranog od OH, O-C1-6 alkila, O-C1-6 haloalkila, CN, NO2, N(RA)RB, C(O)N(RA)RB, C(O)RA, CO2RA, SRA, S(O)RA, S(O)2RA, S(O)2N(RA)RB, N(RA)C(O)RB, N(RA)CO2RB, N(RA)S(O)2RB, N(RA)S(O)2N(RA)RB, OC(O)N(RA)RB, N(RA)C(O)N(RA)RB, N(RA)C(O)C(O)N(RA)RB, CycB, ArilB i HetB,
(5) O-C1-6 haloalkila, izborno dodatno supstituiranog sa jednim ili više supstituenata do maksimalnog broja dozvoljenog valentnošću izabranog od OH, O-C1-6 alkila, O-C1-6 haloalkila, CN, NO2, N(RA)RB, C(O)N(RA)RB, C(O)RA, CO2RA, SRA, S(O)RA, S(O)2RA, S(O)2N(RA)RB, N(RA)C(O)RB, N(RA)CO2RB, N(RA)S(O)2RB, N(RA)S(O)2N(RA)RB, OC(O)N(RA)RB, N(RA)C(O)N(RA)RB, N(RA)C(O)C(O)N(RA)RB, CycB, ArilB i HetB,
(6) halogena,
(7) CN,
(8) NO2,
(9) N(RA)RB,
(10) C(O)N(RA)RB,
(11) C(O)RA,
(12) C(O)-C1-6 haloalkila,
(13) C(O)ORA,
(14) OC(O)RA,
(15) OC(O)N(RA)RB,
(16) SRA,
(17) S(O)RA,
(18) S(O)2RA,
(19) S(O)2N(RA)RB,
(20) N(RA)S(O)2RB,
(21) N(RA)S(O)2N(RA)RB,
(22) N(RA)C(O)RB,
(23) N(RA)C(O)N(RA)RB,
(24) N(RA)C(O)-C(O)N(RA)RB,
(25) N(RA)CO2RB,
(26) N(RC)RD,
(27) C(O)N(RC)RD,
(28) OC(O)N(RC)RD,
(29) S(O)2N(RC)RD,
(30) N(RA)S(O)2N(RC)RD,
(31) N(RA)C(O)N(RC)RD,
(32) N(RA)C(O)-C(O)N(RC)RD,
(33) OH,
(34) CycB,
(35) ArilB,
(36) HetB,
(37) -J-CycB,
(38) -J-ArilB, i
(39) -J-HetB,
ili R4 i R5 na susjednim atomima mogu biti spojeni zajedno sa atomima za koje su vezani tako da formiraju fuzionirani CycC, ArilC ili HetC;
CycA, CycB i CycC su neovisno karbociklil koji je C3-8 cikloalkil, C5-8 cikloalkenil ili C7-12 bicikličan, zasićeni ili nezasićeni, nearomatičan sustav prstena u kojem je jedan prsten fuzioniran za ili premošćen sa drugim prstenom; pri čemu je karbociklil izborno supstituiran sa ukupno od 1 do 6 supstituenata, pri čemu:
(i) od nula do 6 supstituenata su svaki neovisno:
(1) halogen,
(2) CN,
(3) C1-6 alkil,
(4) OH,
(5) O-C1-6 alkil,
(6) C1-6 haloalkil,
(7) O-C1-6 haloalkil,
(8) C1-6 alkenil, ili
(9) C1-6 alkenil supstituiran sa CN, i
(ii) od nula do 2 supstituenta su svaki neovisno:
(1) CycQ,
(2) AriQ,
(3) HetQ,
(4) HetR,
(5) J-CycQ,
(6) J-AriQ,
(7) J-HetQ,
(8) J-HetR,
(9) C1-6 alkil supstituiran sa CycQ, AriQ, HetQ, HetR, J-CycQ, J-AriQ, J-HetQ, ili J-HetR,
(10) C2-6 alkenil supstituiran sa CycQ, AriQ, HetQ, HetR, J-CycQ, J-AriQ, J-HetQ, ili J-HetR, ili
(11) C2-6 alkinil supstituiran sa CycQ, AriQ, HetQ, HetR, J-CycQ, J-AriQ, J-HetQ, ili J-HetR;
ArilA, ArilB i ArilC su neovisno aril koji je izborno supstituiran sa ukupno od 1 do 8 supstituenata, pri čemu:
(i) od nula do 8 supstituenata su svaki neovisno:
(1) C1-6 alkil,
(2) C1-6 haloalkil, koji je izborno supstituiran sa 1 do 3 dodatna supstituenta od kojih je svaki neovisno izabran od OH, O-C1-6 alkila, O-C1-6 haloalkila, CN, NO2, N(RA)RB, C(O)N(RA)RB, C(O)RA, CO2RA, SRA, S(O)RA, S(O)2RA, S(O)2N(RA)RB, N(RA)C(O)RB, N(RA)CO2RB, N(RA)S(O)2RB, N(RA)S(O)2N(RA)RB, OC(O)N(RA)RB, N(RA)C(O)N(RA)RB, ili N(RA)C(O)C(O)N(RA)RB,
(3) C1-6 alkila supstituiranog sa od 1 do 3 supstituenta od kojih je svaki neovisno izabran od OH, O-C1-6 alkila, O-C1-6 haloalkila, CN, NO2, N(RA)RB, C(O)N(RA)RB, C(O)RA, CO2RA, SRA, S(O)RA, S(O)2RA, S(O)2N(RA)RB, N(RA)C(O)RB, N(RA)CO2RB, N(RA)S(O)2RB, N(RA)S(O)2N(RA)RB, OC(O)N(RA)RB, N(RA)C(O)N(RA)RB, ili N(RA)C(O)C(O)N(RA)RB,
(4) C2-6 alkenil,
(5) C2-6 alkenil supstituiran sa od 1 do 3 supstituenta od kojih je svaki neovisno OH, O-C1-6 alkil, O-C1-6 haloalkil, CN, NO2, N(RA)RB, C(O)N(RA)RB, C(O)RA, CO2RA, SRA, S(O)RA, S(O)2RA, S(O)2N(RA)RB, N(RA)C(O)RB, N(RA)CO2RB, N(RA)S(O)2RB, N(RA)S(O)2N(RA)RB, OC(O)N(RA)RB, N(RA)C(O)N(RA)RB, ili N(RA)C(O)C(O)N(RA)RB,
(6) C2-6 alkinil,
(7) C2-6 alkinil supstituiran sa od 1 do 3 supstituenta od kojih je svaki neovisno OH, O-C1-6 alkil, O-C1-6 haloalkil, CN, NO2, N(RA)RB, C(O)N(RA)RB, C(O)RA, CO2RA, SRA, S(O)RA, S(O)2RA, S(O)2N(RA)RB, N(RA)C(O)RB, N(RA)CO2RB, N(RA)S(O)2RB, N(RA)S(O)2N(RA)RB, OC(O)N(RA)RB, N(RA)C(O)N(RA)RB, ili N(RA)C(O)C(O)N(RA)RB,
(8) O-C1-6 alkil,
(9) O-C1-6 haloalkil,
(10) OH,
(11) halogen,
(12) CN,
(13) NO2,
(14) N(RA)RB,
(15) C(O)N(RA)RB,
(16) C(O)RA,
(17) C(O)-C1-6 haloalkil,
(18) C(O)ORA,
(19) OC(O)N(RA)RB,
(20) SRA,
(21) S(O)RA,
(22) S(O)2RA,
(23) S(O)2N(RA)RB,
(24) N(RA)S(O)2RB,
(25) N(RA)S(O)2N(RA)RB,
(26) N(RA)C(O)RB,
(27) N(RA)C(O)N(RA)RB,
(28) N(RA)C(O)-C(O)N(RA)RB,
ili
(29) N(RA)CO2RB,
i
(ii) od nula do 2 supstituenta su svaki neovisno:
(1) CycQ,
(2) AriQ,
(3) HetQ,
(4) HetR,
(5) J-CycQ,
(6) J-AriQ,
(7) J-HetQ,
(8) J-HetR,
(9) C1-6 alkil supstituiran sa CycQ, AriQ, HetQ, HetR, J-CycQ, J-AriQ, J-HetQ, ili J-HetR,
(10) C2-6 alkenil supstituiran sa CycQ, AriQ, HetQ, HetR, J-CycQ, J-AriQ, J-HetQ, ili J-HetR, ili
(11) C2-6 alkinil supstituiran sa CycQ, AriQ, HetQ, HetR, J-CycQ, J-AriQ, J-HetQ, ili J-HetR;
HetA, HetB i HetC su neovisno heterociklil ili heteroaril koji je izborno supstituiran sa ukupno od 1 do 8 supstituenata, gdje:
(i) od nula do 8 supstituenata su svaki neovisno:
(1) C1-6 alkil,
(2) C1-6 haloalkil, koji je izborno supstituiran sa 1 do 3 dodatna supstituenta od kojih je svaki neovisno izabran od OH, O-C1-6 alkila, O-C1-6 haloalkila, CN, NO2, N(RA)RB, C(O)N(RA)RB, C(O)RA, CO2RA, SRA, S(O)RA, S(O)2RA, S(O)2N(RA)RB, N(RA)C(O)RB, N(RA)CO2RB, N(RA)S(O)2RB, N(RA)S(O)2N(RA)RB, OC(O)N(RA)RB, N(RA)C(O)N(RA)RB, ili N(RA)C(O)C(O)N(RA)RB,
(3) C1-6 alkil supstituiran sa od 1 do 3 supstituenta od kojih je svaki neovisno izabran od OH, O-C1-6 alkila, O-C1-6 haloalkila, CN, NO2, N(RA)RB, C(O)N(RA)RB, C(O)RA, CO2RA, SRA, S(O)RA, S(O)2RA, S(O)2N(RA)RB, N(RA)C(O)RB, N(RA)CO2RB, N(RA)S(O)2RB, N(RA)S(O)2N(RA)RB, OC(O)N(RA)RB, N(RA)C(O)N(RA)RB, ili N(RA)C(O)C(O)N(RA)RB,
(4) C2-6 alkenil,
(5) C2-6 alkenil supstituiran sa od 1 do 3 supstituenta od kojih je svaki neovisno OH, O-C1-6 alkil, O-C1-6 haloalkil, CN, NO2, N(RA)RB, C(O)N(RA)RB, C(O)RA, CO2RA, SRA, S(O)RA, S(O)2RA, S(O)2N(RA)RB, N(RA)C(O)RB, N(RA)CO2RB, N(RA)S(O)2RB, N(RA)S(O)2N(RA)RB, OC(O)N(RA)RB, N(RA)C(O)N(RA)RB, ili N(RA)C(O)C(O)N(RA)RB,
(6) C2-6 alkinil,
(7) C2-6 alkinil supstituiran sa od 1 do 3 supstituenta od kojih je svaki neovisno OH, O-C1-6 alkil, O-C1-6 haloalkil, CN, NO2, N(RA)RB, C(O)N(RA)RB, C(O)RA, CO2RA, SRA, S(O)RA, S(O)2RA, S(O)2N(RA)RB, N(RA)C(O)RB, N(RA)CO2RB, N(RA)S(O)2RB, N(RA)S(O)2N(RA)RB, OC(O)N(RA)RB, N(RA)C(O)N(RA)RB, ili N(RA)C(O)C(O)N(RA)RB,
(8) O-C1-6 alkil,
(9) O-C1-6 haloalkil,
(10) OH,
(11) okso,
(12) halogen,
(13) CN,
(14) NO2,
(15) N(RA)RB,
(16) C(O)N(RA)RB,
(17) C(O)RA,
(18) C(O)-C1-6 haloalkil,
(19) C(O)ORA,
(20) OC(O)N(RA)RB,
(21) SRA,
(22) S(O)RA,
(23) S(O)2RA,
(24) S(O)2N(RA)RB,
(25) N(RA)S(O)2RB,
(26) N(RA)S(O)2N(RA)RB,
(27) N(RA)C(O)RB,
(28) N(RA)C(O)N(RA)RB,
(29) N(RA)C(O)-C(O)N(RA)RB,
ili
(30) N(RA)CO2Rb,
i
(ii) od nula do 2 supstituenta su svaki neovisno:
(1) CycQ,
(2) AriQ,
(3) HetQ,
(4) HetR,
(5) J-CycQ,
(6) J-AriQ,
(7) J-HetQ,
(8) J-HetR,
(9) C1-6 alkil supstituiran sa CycQ, AriQ, HetQ, HetR, J-CycQ, J-AriQ, J-HetQ, ili J-HetR,
(10) C2-6 alkenil supstituiran sa CycQ, AriQ, HetQ, HetR, J-CycQ, J-AriQ, J-HetQ, ili J-HetR, ili
(11) C2-6 alkinil supstituiran sa CycQ, AriQ, HetQ, HetR, J-CycQ, J-AriQ, J-HetQ, ili J-HetR;
svaki CycQ je neovisno C3-8 cikloalkil ili C5-8 cikloalkenil, pri čemu cikloalkil ili cikloalkenil je izborno supstituiran sa od 1 do 4 supstituenta, od kojih je svaki neovisno halogen, C1-6 alkil, OH, O-C1-6 alkil, C1-6 haloalkil ili O-C1-6 haloalkil;
svaki AriQ je neovisno fenil ili naftil, gdje je fenil ili naftil izborno supstituiran sa od 1 do 5 supstituenata od kojih je svaki neovisno halogen, CN, NO2, C1-6 alkil, C1-6 haloalkil, OH, O-C1-6 alkil, O-C1-6 haloalkil, N(RA)RB, C(O)N(RA)RB, C(O)RA, CO2RA, SRA, S(O)RA, SO2RA, SO2N(RA)RB ili SO2N(RA)C(O)RB;
svaki HetQ je neovisno heteroaril koji je izborno supstituiran sa od 1 do 4 supstituenta od kojih je svaki neovisno halogen, C1-6 alkil, C1-6 haloalkil, OH, O-C1-6 alkil, O-C1-6 haloalkil, N(RA)RB, C(O)N(RA)RB, C(O)RA, CO2RA, SO2RA, N(RA)C(O)N(RA)RB ili N(RA)CO2RB;
svaki HetR je neovisno 4- do 7-člani, zasićeni ili nezasićeni, nearomatični heterociklični prsten koji sadrži najmanje jedan atom ugljika i od 1 do 4 heteroatoma neovisno izabrana od N, O i S, gdje je svaki S izborno oksidiran do S(O) ili S(O)2, i gdje je zasićeni ili nezasićeni heterociklični prsten izborno supstituiran sa od 1 do 4 supstituenta od kojih je svaki neovisno halogen, CN, C1-6 alkil, OH, okso, O-C1-6 alkil, C1-6 haloalkil, O-C1-6 haloalkil, C(O)N(RA)RB, C(O)RA, CO2RA, ili SO2RA;
svaki J je neovisno:
(i) O,
(ii) S,
(iii) S(O),
(iv) S(O)2,
(v) O-C1-6 alkilen,
(vi) S-C1-6 alkilen,
(vii) S(O)-C1-6 alkilen,
(viii) S(O)2-C1-6 alkilen,
(ix) N(RA), ili
(x) N(RA)-C1-6 alkilen;
svaki RA, RB, RC i RD su neovisno izabrani od H, C1-6 alkila i C3-6cikloalkila, pri čemu su navedeni C1-6 alkil i C3-6cikloalkil izborno supstituirani sa jednim ili više supstituenata do maksimalnog broja dozvoljenog valentnošću izabranog iz grupe koja se sastoji od: halogena, OH, CN, C1-4alkoksi, C3-6cikloalkila i fenila;
ili alternativno svaki par RC i RD zajedno sa dušikom za koji su oba vezani formiraju 4- do 7-člani zasićeni ili mono-nezasićeni prsten koji izborno sadrži heteroatom pored N za koji su RC i RD vezani, pri čemu je dodatni heteroatom izabran od N, O i S; pri čemu je prsten izborno supstituiran sa 1 ili 2 supstituenta od kojih je svaki neovisno C1-6 alkil, C(O)RA, C(O)ORA, C(O)N(RA)RB ili S(O)2RA; i pri čemu je izborni S u prstenu izborno u obliku S(O) ili S(O)2
svaki aril je neovisno (i) fenil, (ii) 9- ili 10-člani biciklični, fuzionirani karbociklični sustav prstena u kojem je najmanje jedan prsten aromatičan, ili (iii) 11- do 14-člani tricikličan, fuzionirani karbocikličan sustav prstena u kojem je najmanje jedan prsten aromatičan;
svaki heterociklil je neovisno (i) 4- do 8-člani, zasićeni ili nezasićeni monociklični prsten, (ii) 7- do 12-člani biciklični sustav prstena, ili (iii) 10- do 18-člani tricikličan sustav prstena, gdje je svaki prsten u (ii) ili (iii) neovisan od, fuzioniran sa ili premošćen sa drugim prstenom ili prstenovima i svaki prsten je zasićen ili nezasićen; gdje monocikličan prsten sadrži od 1 do 4 heteroatoma i ravnotežu atoma ugljika; bicikličan sustav prstena ili tricikličan sustav prstena sadrži od 1 do 8 heteroatoma i ravnotežu atoma ugljika, gdje jedan ili više od prstenova sadrže jedan ili više od heteroatoma; gdje su heteroatomi izabrani od N, O i S; i gdje su bilo koji ili više od heteroatoma dušika i sumpora izborno oksidirani, i bilo koji ili više od heteroatoma dušika je izborno kvaterniziran;
svaki heteroaril je neovisno (i) 5- ili 6-člani heteroaromatični prsten koji sadrži od 1 do 4 heteroatoma neovisno izabrana od N, O i S, gdje je svaki N izborno u obliku oksida, ili (ii) 9- ili 10-člani heterobicikličan, fuzionirani sustav prstena koji sadrži od 1 do 6 heteroatoma neovisno izabrana od N, O i S, gdje bilo koji ili oba prstena sadrže jedan ili više od heteroatoma, najmanje jedan prsten je aromatičan, svaki N je izborno u obliku oksida i svaki S u prstenu koji nije aromatičan je izborno S(O) ili S(O)2.
2. Kombinacija prema patentnom zahtjevu 1, naznačena time što spoj formule (Ia) je izabrano od:
[image]
i
[image]
ili njegove farmaceutski prihvatljive soli.
3. Kombinacija prema patentnom zahtjevu 2, naznačena time što spoj formule (Ia) je:
[image]
ili njegova farmaceutski prihvatljiva sol.
4. Kombinacija prema patentnom zahtjevu 2, naznačena time što spoj formule (Ia) je:
[image]
ili njegova farmaceutski prihvatljiva sol.
5. Kombinacija prema patentnom zahtjevu 2, naznačena time što spoj formule (Ia) je:
[image]
ili njegova farmaceutski prihvatljiva sol.
6. Kombinacija prema patentnom zahtjevu 2, naznačena time što spoj formule (Ia) je:
[image]
ili njegova farmaceutski prihvatljiva sol.
7. Kombinacija prema patentnom zahtjevu 2, naznačena time što spoj formule (Ia) je:
[image]
ili njegova farmaceutski prihvatljiva sol.
8. Kombinacija prema bilo kojem od patentnih zahtjeva 1-7, naznačena time što jedno ili više sredstava protiv HIV-a je antivirusno sredstvo izabrano od inhibitora HIV proteaze, nukleozidnih inhibitora HIV reverzne transkriptaze, nenukleozidnih inhibitora HIV reverzne transkriptaze, inhibitora HIV integraze, inhibitora fuzije HIV-a i inhibitora ulaska HIV-a.
9. Kombinacija prema bilo kojem od patentnih zahtjeva 1-7, naznačena time što su jedan ili više sredstava protiv HIV-a izabrani od:
abakavir,
abakavir +lamivudin,
abakavir + lamivudin + zidovudin,
amprenavir,
atazanavir,
zidovudin,
kapravirin
darunavir,
zalcitabin,
didanozin,
gastrorezistentno obložen didanozin,
delavirdin,
efavirenc,
efavirenc + emtricitabin + tenofovir disoproksil fumarat,
4’-etinil-2-fluoro-2’-deoksiadenozin
emtricitabin,
emtricitabin + tenofovir disoproksil fumarat,
emvirin,
enfuvirtid,
etravirin,
fosamprenavir kalcij,
indinavir,
lamivudin,
lamivudin + zidovudin,
lopinavir
lopinavir + ritonavir,
maravirok,
nelfinavir,
nevirapin,
PPL-100
raltegravir,
ritonavir,
sakvinavir,
stavudin,
tenofovir disoproksil fumarat,
tenofovirheksadeciloksipropil
tipranavir,
abakavir sulfat,
delavirdin mezilat,
indinavir sulfat,
atazanavir sulfat,
nelfinavir mezilat i
sakvinavir mezilat
10. Kombinacija prema patentnom zahtjevu 9, naznačena time što jedno ili više anti-HIV sredstava je 4'-etinil-2-fluoro-2'-deoksiadenozin.
11. Farmaceutska kompozicija koja sadrži kombinaciju prema bilo kojem od patentnih zahtjeva 1-10 i farmaceutski prihvatljiv nosač.
12. Kombinacija prema bilo kojem od patentnih zahtjeva 1-10, za uporabu u inhibiciji HIV reverzne transkriptaze kod subjekta.
13. Kombinacija prema bilo kojem od patentnih zahtjeva 1-10, za uporabu u profilaksi infekcije HIV-om ili profilaksi SIDA-e kod subjekta.
14. Kombinacija prema bilo kojem od patentnih zahtjeva 1-10, za uporabu u liječenju infekcije HIV-om, liječenju SIDA-e, ili odlaganju početka SIDA-e kod subjekta.
15. Kombinacija za uporabu prema bilo kojem od patentnih zahtjeva 12-14, naznačena time što subjekt je čovjek.
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